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Preexisting Serum Autoantibodies Against the NMDAR Subunit NR1 Modulate Evolution of Lesion Size in Acute Ischemic Stroke.
Zerche, Maria; Weissenborn, Karin; Ott, Christoph; Dere, Ekrem; Asif, Abdul R; Worthmann, Hans; Hassouna, Imam; Rentzsch, Kristin; Tryc, Anita B; Dahm, Liane; Steiner, Johann; Binder, Lutz; Wiltfang, Jens; Sirén, Anna-Leena; Stöcker, Winfried; Ehrenreich, Hannelore.
Afiliação
  • Zerche M; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Weissenborn K; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Ott C; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Dere E; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Asif AR; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Worthmann H; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Hassouna I; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Rentzsch K; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Tryc AB; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Dahm L; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Steiner J; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Binder L; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Wiltfang J; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Sirén AL; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Stöcker W; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
  • Ehrenreich H; From the Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany (M.Z., C.O., E.D., I.H., L.D., H.E.); Department of Neurology, Hannover Medical School, Hannover, Germany (K.W., H.W., A.B.T.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain,
Stroke ; 46(5): 1180-6, 2015 May.
Article em En | MEDLINE | ID: mdl-25765725
ABSTRACT
BACKGROUND AND

PURPOSE:

Recently, we reported high seroprevalence (age-dependent up to >19%) of N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) autoantibodies in both healthy and neuropsychiatrically ill subjects (N=4236). Neuropsychiatric syndrome relevance was restricted to individuals with compromised blood-brain barrier, for example, apolipoprotein E4 (APOE4) carrier status, both clinically and experimentally. We now hypothesized that these autoantibodies may upon stroke be protective in individuals with hitherto intact blood-brain barrier, but harmful for subjects with chronically compromised blood-brain barrier.

METHODS:

Of 464 patients admitted with acute ischemic stroke in the middle cerebral artery territory, blood for NMDAR1 autoantibody measurements and APOE4 carrier status as indicator of a preexisting leaky blood-brain barrier was collected within 3 to 5 hours after stroke. Evolution of lesion size (delta day 7-1) in diffusion-weighted magnetic resonance imaging was primary outcome parameter. In subgroups, NMDAR1 autoantibody measurements were repeated on days 2 and 7.

RESULTS:

Of all 464 patients, 21.6% were NMDAR1 autoantibody-positive (immunoglobulin M, A, or G) and 21% were APOE4 carriers. Patients with magnetic resonance imaging data available on days 1 and 7 (N=384) were divided into 4 groups according to NMDAR1 autoantibody and APOE4 status. Groups were comparable in all stroke-relevant presenting characteristics. The autoantibody+/APOE4- group had a smaller mean delta lesion size compared with the autoantibody-/APOE4- group, suggesting a protective effect of circulating NMDAR1 autoantibodies. In contrast, the autoantibody+/APOE4+ group had the largest mean delta lesion area. NMDAR1 autoantibody serum titers dropped on day 2 and remounted by day 7.

CONCLUSIONS:

Dependent on blood-brain barrier integrity before an acute ischemic brain injury, preexisting NMDAR1 autoantibodies seem to be beneficial or detrimental.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Isquemia Encefálica / Receptores de N-Metil-D-Aspartato / Acidente Vascular Cerebral Tipo de estudo: Etiology_studies / Observational_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Stroke Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Isquemia Encefálica / Receptores de N-Metil-D-Aspartato / Acidente Vascular Cerebral Tipo de estudo: Etiology_studies / Observational_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Stroke Ano de publicação: 2015 Tipo de documento: Article